title: Resuscitation after prolonged cardiac arrest: effects of cardiopulmonary bypass and sodium-hydrogen exchange inhibition on myocardial and neurological recovery.
abstract: OBJECTIVE
  To determine if cardiopulmonary bypass (CPB), together with inhibition of the sodium-hydrogen exchanger (NHE), limits myocardial and neurological injury and improves recovery after prolonged (unwitnessed) cardiac arrest (CA), as NHE inhibition improved recovery after deep hypothermic circulatory arrest.
  
  
  METHODS
  Twenty-seven pigs (31-39 kg) underwent 15 min of prolonged (no-flow) CA followed by 10 min of cardiopulmonary resuscitation-advanced life support (CPR-ALS). Subjects with restoration of spontaneous circulation (ROSC) during CPR-ALS received either no drug (n=6) or an inhibitor of the NHE (HOE-642; n=5). In the 16 unsuccessfully resuscitated animals, peripheral normothermic CPB was instituted, and either no drug (n=9) or similar HOE-642 (n=7) therapy started. Hemodynamic data, a species-specific neurological deficit score (0=normal to 500=brain death), and mortality were recorded at 24h, and biochemical variables of organ injury measured.
  
  
  RESULTS
  CPR-ALS restored ROSC in 41% (11/27) of animals, but was unsuccessful in 59% (16/27) that required CPB. Without CPB, HOE-642 increased cardiac index and decreased vascular resistance; with CPB, HOE-642 caused higher pump flows (3.4±0.6 l min(-1)m(-2) vs 2.5±0.7 l min(-1)m(-2); p<0.001) and higher post-arrest cardiac index; but animals required more vasopressors (p=0.019) from drug-induced vasodilation. No differences between biochemical markers of oxidative and organ injury and overall 24-h mortality (20%) were found between groups. Neurological score was improved at 24h compared with 4h only after HOE-642 treatment with (150±34 vs 220±43; p=0.003) or without CPB (162±39 vs 238±48; p≤0.001), but failed to reach statistical difference with respect to the untreated group.
  
  
  CONCLUSIONS
  CPB is an effective resuscitative tool to treat prolonged CA but there is limited improvement of neurological function. NHE inhibition augments cardiac and neurological function, but its effect was less pronounced than in other studies.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Liakopoulos
authors.forename: Nikola
authors.initials: N
authors.lastname: Hristov
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Buckberg
authors.forename: Jonathan
authors.initials: J
authors.lastname: Triana
authors.forename: Georg
authors.initials: G
authors.lastname: Trummer
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Allen
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass / Q000379:methods*; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D006323:Heart Arrest / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control*; D012640:Seizures / Q000209:etiology / Q000628:therapy; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use; D034421:Sus scrofa; D016896:Treatment Outcome
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide